Genetic factors are well-recognized to play an important role in the pathogenesis of Alzheimer's disease (AD). This is best unerstood for the genes causing early onset familial AD (EOAD), namely APP, PS1 and PS2. A single genetic factor influencing age of onset in late onset AD (LOAD) is also recognized, namely ApoE. Nevertheless, there still exist large gaps in our understanding of the genetic aspects of AD including additional genetic factors impacting age of onset, penetrance and phenotypic expression of both EAOD and LOAD. Furthermore, it is clear that many other types of hereditary dementia overlap clinically, pathologically and molecularly with AD, as well as being important in their own right. The purpose of the UW ADRC Genetics Core is to provide a unique resource of family material and genotyping information to qualified investigators to advance our understanding of genetic factors in AD and other dementing illnesses. The Specific Aims are: Specific Aim 1: To recruit, characterize, sample and follow families with Alzheimer's disease and other forms of dementia. Phenotypic data and samples from these families will be made available to investigators in the U W ADRC and other appropriate scientists at the University of Washington and other institutions. Specific Aim 2: Provide serum/plasma/DNA banking for studies of AD and other dementias. Specific Aim 3: Provide genotyping and mutational analysis for AD and dementia studies including (a) apolipoprotein (APOE) genotyping, (b) APOE haplotyping for 20 SNP sites including promoter polymorphisms and (c) mutation screening for known dementia genes including presenilins 1 and 2 (PSEN1,PSEN2), the prion gene (PRNP), MAPT (gene for tau), a-synuclein (ASN), parkin and DJ-1. Specific Aim 4: Provide genotyping and mutational anlysis for new dementia genes and polymorphic sites identified other AD investigators. Materials and information from this Core will be made available to collaborators within the UW ADRC, the UW Health Sciences Complex and all other relevant investigators in the US and worldwide.